Researchers have designed a new blood-thinning compound that can prevent blood clots without a significant risk of bleeding, which is a common side effect of existing blood-thinners.
A thrombosis occurring in the coronary artery can interrupt blood flow to the heart, resulting in a heart attack.
In situations such as this, doctors must administer rapid treatment to resolve the blood clot and save a person’s life.
Blood-thinning agents, or anticoagulants, such as heparin, help the body break down clots in the blood and prevent additional clots from forming.
However, anticoagulant agents prevent the enzymes that help stop bleeding from working. This can lead to a significant risk of bleeding, which can be life threatening.
In a new study, researchers from the Ecole Polytechnique Fédérale de Lausanne (EPFL) in Switzerland describe a new type of blood thinner that resolves thrombosis, without a risk of major bleeds.
Although experiments in mice, rabbits, and pigs show the molecule to be stable, safe, and effective, scientists need to conduct further research before doctors can use it in people.
The study appears in the journal Nature Communications.
The new blood thinner works by inhibiting coagulation factor XII (FXII), which kicks off the blood-clotting process.
Scientists know that targeting this molecule is safe because humans that naturally lack FXII are at less risk of thrombosis but do not bleed more than normal. Studies in mice without FXII also show this to be accurate, and other studies in rats, rabbits, and primates also confirm the evidence.
Although this study is not the first to successfully create an inhibitor of FXII, doctors have not been able to use previous compounds because they do not have sufficient potency or selectivity.
In this study, the researchers made some small but significant changes to a previously designed inhibitor — called FXII618 — to make it a viable treatment option.
Using a combination of random screening approaches and rational design, they identified parts of the molecule that they could change. They strengthened its binding capacity by more than 20 times and increased its stability in the blood 25-fold.
After completing this painstaking design process, the team collaborated with experts in disease modeling at the University of Bern in Switzerland to test the drug in animals.
Experiments in mice, rabbits, and pigs revealed important properties of the molecule, such as the dose needed for it to be effective. The experiments also confirmed that it was safe and showed no signs of toxicity.
Further experiments in a mouse model of thrombosis showed that the inhibitor could effectively treat blood clots without increasing the risk of bleeding.
“Our collaboration found that it is possible to achieve bleeding-free anti-coagulation with a synthetic inhibitor.”
– Prof. Christian Heinis, Laboratory of Therapeutic Proteins and Peptides, EPFL
In the final set of experiments, the researchers tested the inhibitor in an artificial lung model. Doctors use artificial lungs to keep a person alive when their lungs are unable to do so, for example, between lung failure and receiving a transplant.
Artificial lungs can help keep people alive in life threatening situations, such as severe cases of COVID-19. However, they also increase the risk of blood clots.
“In these devices, contact of blood proteins with artificial surfaces, such as the membrane of the oxygenator or tubing, can cause blood clotting,” senior author of the study Prof. Heinis explains. This process, called contact activation, can lead to dangerous complications and may even be fatal.
In a rabbit model of an artificial lung, the team found that the new blood thinner prolonged important blood clotting parameters around 10-fold, which is five times more effective than heparin.
Rabbits who received the new blood thinner also showed completely normal bleeding, while those treated with heparin bled longer than normal.
Overall, the findings suggest that the new blood thinner could offer safe protection against blood clots in patients receiving artificial lung treatment.
Although these results are encouraging, the blood-thinner does not stay in the body for very long. In rabbits, the body eliminates the compound within 30 minutes.
This means that doctors would need to infuse it continuously for it to have any effect. For the drug to be a viable alternative to other anticoagulants, the researchers are designing new variants with longer retention times.
It is also important to note that scientists do not intend for people to receive this treatment long-term (over months, weeks, or even days), and a person could not take it by mouth.
Therefore, doctors could only administer this treatment to prevent blood clots during acute procedures, such as bypass surgery or treatment that involves an artificial lung.